Fluid shear stress modulates cytosolic free calcium in vascular endothelial cells

Abstract

Cytosolic free Ca2+ concentration ([Ca2+]i) was monitored in single and groups of fura-2-loaded bovine aortic endothelial cells (BAEC) during exposure to laminar fluid shear stress. Application of a step increase in shear stress from 0.08 to 8 dyn/cm2 to confluent BAEC monolayers resulted in a transient increase in [Ca2+]i, which attained a peak value in 15-40 s, followed by a decline to baseline within 40-80 s. The magnitude of the [Ca2+]i responses increased with applied shear stress over the range of 0.2-4 dyn/cm2 and reached a maximum at greater than 4 dyn/cm2. Transient oscillations in [Ca2+]i with gradually diminishing amplitude were observed in individual cells subjected to continuous high shear stress. Elimination of extracellular Ca2+ with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, blockade of Ca2+ entry with lanthanum, depolarization of the cell membrane with high K+, and preconditioning of BAEC in steady laminar flow had little effect on the [Ca2+]i response. In the presence of ATP or ADP, application of shear stress caused repetitive oscillations in [Ca2+]i in single BAEC, whose frequency was dependent on both agonist concentration and the magnitude of applied shear stress. However, apyrase, an ATPase and ADPase, did not inhibit the shear-induced [Ca2+]i responses in standard medium (no added ATP or ADP), suggesting that the shear-induced [Ca2+]i response is not due to ATP released by endothelial cells.

Atherosclerosis and calcium signalling in endothelial cells

“…It has been reported (Dull and Davies, 1991;Shen et al, 1992) No-load channel constant a=2 Table 2: Parameter values used in the model for calcium dynamics.…”

“…Transduction of an external biochemical or mechanical signal, however, stimulates both a release of Ca 2 + from internal stores and an influx of Ca 2 + across the plasma membrane (Alberts et al, 1994). This can result in a single transient peak of cytosolic Ca 2 + concentration, followed by a return towards baseline, or in sustained Ca 2 + oscillations (Dull and Davies, 1991;Shen et al, 1992). The decay in cytosolic Ca2+ following internal Ca 2 + release is a result of the plasma membrane Ca 2 +-ATPase, which pumps Ca 2 + from the cytosol out of the cell, and the ER Ca2+ -ATPase, which resequesters Ca 2 + from the cytosol back into the ER (Schilling and Elliott, 1992).…”

Force-induced focal adhesion translocation: effects of force amplitude and frequency

“…Mechanotransduction studies with fluid shear stress typically apply stresses on the order of 1-10 dynes/cm 2 (0.1-1.0 Pa) and observe changes in intracellular calcium and nitric oxide levels (22,27,29,38), ion channel activity (2,33), G protein activation (20), gene expression (15), and focal adhesion translocation (30). This level of stress, applied over a typical endothelial cell area on the order of 1,000 m 2 , results in nN-level shear forces.…”

“…Cells exposed to rapidly fluctuating shear stress environments, generated with turbulent flow, do not align with the direction of flow as do cells exposed to laminar fluid shear stress (10), whereas oscillating fluid shear stress with a low mean positive force does not induce the same gene expression as flow with a high mean positive force (15,18,44). Furthermore, ramped levels of laminar fluid shear stress result in graded nitric oxide (29) and intracellular calcium (38) responses. These studies show that the biological response of a cell to mechanical force depends on both the magnitude and time course of applied external force but present little information regarding the physical basis for these observations.…”

A Neurovascular Blood-Flow Modulation Model via Acupuncture Induced Nitric Oxide

“…Periodic bursts of intracellular free Ca 2+ in response to a constant agonist concentration have been observed in a number of non-excitable cell types including endothelial cells [77][78][79]. There is controversy regarding shear stress-induced Ca 2+ transient release in endothelial cells with some investigators reporting multiple Ca 2+ transient events [80][81][82][83], whereas others report only their irregular appearance or nothing at all [84][85][86]. Furthermore, both transient and sustained release of NO has been reported in response to this shear stress.…”